Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143639" target="_blank" >RIV/00216224:14740/25:00143639 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1186/s12943-025-02451-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate" target="_blank" >https://link.springer.com/article/10.1186/s12943-025-02451-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12943-025-02451-2" target="_blank" >10.1186/s12943-025-02451-2</a>

Result language

angličtina

Original language name

Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth

Original language description

Thyroid hormone (TH) signaling plays a major role in the development, energy homeostasis, and metabolism of most tissues. Recent studies have identified THs as drivers of prostate cancer (PCa) development and progression. We reported that the T3-scavenger protein mu -crystallin (CRYM) regulates the development and progression of PCa and that this involved crosstalk with androgen receptor (AR) signaling. However, the mechanisms remain incompletely understood. Here, we explored the role of thyroid hormone receptor beta (TR beta), which is the main effector of TH signaling, in the context of PCa. The use of the TR beta-selective antagonist NH-3 inhibited PCa cell proliferation in vitro and reduced tumor size in PCa xenograft models in vivo. Notably, NH-3 was highly effective in the engrafted 22Rv1 cell line, a model for castration-resistant PCa (CRPC). Mechanistic studies revealed that NH-3 downregulates AR and the AR target genes Nkx3.1 and KLK3 (PSA). NH-3 was a more effective anticancer agent than enzalutamide, and their combined use was synergistic. Evidence from human datasets corroborates our findings, whereby elevated TR beta expression and mutations in the TH signaling pathway are associated with the onset of PCa. Collectively, these results establish TR beta as a mediator of tumorigenesis in PCa and identify NH-3 as a promising therapeutic agent for targeting AR signaling, particularly in CRPC.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

—

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Cancer

ISSN

1476-4598

e-ISSN

1476-4598

Volume of the periodical

24

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

21

Pages from-to

1-21

UT code for WoS article

001594409100001

EID of the result in the Scopus database

2-s2.0-105018653603